The Transgenic and ES Cell Core of the Washington University Diabetes Research Center (DRC) is a shared facility whose goal is the efficient and cost-effective development of genetically-altered mouse models to elucidate the pathogenesis of diabetes and its complications and explore related areas of endocrinology and metabolism. These animal models provide an important avenue for pre-clinical studies that will serve as the basis for translating basic research advances into clinical practice. Importantly, in vivo models allow the analysis of gene function in the context of complex intercellular and integrative systemic responses needed for the study of diabetes, a polygenic disorder involving multiple tissue types and environmental influences. Current molecular genetic techniques allow spatially and temporally restricted analysis of gene effects (both inactivation and over-expression) in mice using altered systems alone or in combination, leading to previously unprecedented creativity and resolution in analysis. Although the concepts involved in generating transgenic (Tg) or knockout/knockin (KO/KI) animals are in general straightforward, the equipment, facilities, and personnel with the appropriate technical skills are either impractical or too expensive for most labs to implement independently. With continued enthusiastic demand for assistance in the generation of genetically altered mice, the DRC Transgenic and ES Cell Core will continue to provide the necessary expertise, facilities, equipment, and personnel to efficiently generate Tg and KO/KI mice for DRC members and assist in propagating pooriy breeding animals. Additional services include marker assisted generation of congenic lines and transient Cre of FLP recombinase expression in zygotes by microinjection of expression plasmids. To accomplish this, the Core will utilize pre-existing, in-house, highly successful facilities - the Washington University Transgenic Vectors Core, Siteman Cancer Center ES Cell Core, and Mouse Genetics Core. Utilization of these facilities for vector design/construction, electroporation, and DNA/ES cell microinjection precludes the need for the Transgenic and ES Cell Core to purchase and set up expensive equipment and independently hire/train/manage our own personnel.